The following is a summary of “Mechanistic Insights and the Clinical Prospects of targeted therapies for glioblastoma: a comprehensive review,” published in the April 2024 issue of Hematology by Shen et al.
Glioblastoma (GBM), a devastating brain tumor traditionally diagnosed based on histological criteria, has seen a significant shift in classification owing to recent molecular profiling studies. These investigations have led to a redefinition of central nervous system tumor classification by the World Health Organization, incorporating pivotal pathogenetic markers. In-depth molecular analyses have unveiled a landscape of dysregulated oncogenic pathways underlying GBM’s aggressiveness and resistance mechanisms. This newfound understanding of GBM’s molecular vulnerabilities has catalyzed a paradigm shift in disease management, pivoting from conventional chemotherapy toward targeted therapies.
Emerging targeted drugs aim to thwart various oncogenic targets implicated in GBM, encompassing receptors within the angiogenic axis, the signal transducer and activator of transcription 3 (STAT3), the PI3K/AKT/mTOR signaling cascade, the ubiquitination-proteasome pathway, and IDH1/2 pathways. While promising outcomes have been observed with certain targeted agents in preclinical settings, their clinical translation in GBM treatment remains challenging.
Researchers delve into recent advancements and clinical evaluations of targeted therapeutics, exploring the potential of cell-based therapies and combinatorial treatment strategies as novel avenues for GBM management. Although targeted treatments exhibit superior preclinical efficacy compared to traditional chemotherapy, their clinical effectiveness is impeded by obstacles such as limited blood-brain barrier penetrance. Consequently, the development of combinatorial targeted therapies holds promise for enhancing therapeutic outcomes and surmounting drug resistance in GBM management.
Source: ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00512-8